6.03 Stroke

Front 1

What are some differences between collapse caused by syncope, epilepsy and cerebrovascular problems?

Back 1

- Syncope -> very brief and sudden. Rapid and complete recovery
- Epilepsy -> afterwards they're confused. Usually lasts less than 2 minutes
- Stroke -> collapse is usually of longer duration than the other two. And afterwards they have neurological deficits

Front 2

Where is the inf cerebellar peduncle?

Back 2

Open medulla

Front 3

Via what tract does the BRF control viscera?

Back 3

The reticulospinal tract

Front 4

What does PICA come off?

Back 4

The vertebral artery

Front 5

what does vertebral artery come off?

Back 5

Subclavian artery

Front 6

What are the three arteries supplying the closed medulla?

Back 6

- Anterior spinal
- Vertebral
- Posterior spinal

Front 7

What are the three arteries supplying the open medulla?

Back 7

- Anterior spinal
- Vertebral
- PICA

Front 8

What are the three arterires supplying the pons?

Back 8

- Basilar artery - paramedian branches
- Basilar artery - circumferential arteries
- AICA

Front 9

Over what range of perfusion pressures does cerebral perfusion remain constant?

Back 9

50-150mmHg

Front 10

If arterial BP drops, what will the cerebral vessels do? HOW?

Back 10

They will dilate to increase cerebral perfusion
Regulated by local CO2 levels (increased -> vasodilation to clear the CO2 away)

Front 11

Does the ANS play a big role in control of cerebral blood flow under normal conditions?

Back 11

NO!

Front 12

When does ANS control of cerebral blood flow play an impt role?

Back 12

- Above 150mmHg perfusion pressure, symp innervation of the BVs is believed to help further constrict the vessels
- Parasymp fibres dilate vessels under conditions of focal hypoxia or ischaemia in the brain

Front 13

Two classes of types of strokes? most common?

Back 13

Infarction (most common) and haemorrhage

Front 14

List and describe the 6 main causes of stroke

Back 14

- Atherthrombosis (can occur in the ICA in the neck = extracranial. Or in the intracranial vessels)
- Embolism (when clot breaks off from elsewhere and lodges in the brain)
- Lacunar infarcts (small penetrating arteries supplying deep brain structures are occluded. Associated with hypertension)
- Global hypoperfusion -> boundary / watershed infarcts
- Intracerebral haemorrhage (rupture of small artery, associated with hypertension)
- Subarachnoid haemorrhage (Berry aneurysms in the anterior cerebral circulation = most common)

Front 15

What are the cellular events that happen in the brain following ischaemia?

Back 15

Decreased O2 -> decreased ATP --> Na/K ATPase pump fails (and the Na+ chs start to malfunction -> increased opening time) --> breakdown the normal Na+ gradient
This stuffs up the transporters of glutamate and aspartate (excitatory aas) -> the transporters run backwards --> increased glutamate/aspartate in extracellular space -> increased activation of NMDA / AMPA Rs -> increased Ca2+ influx into the cell. PLUS the Ca2+ ATPase (pumping Ca2+ out of teh cell) fails without enough ATP --> further increase in Ca2+ in the cell --> activation of proteases, lipases, endonucleases etc etc --> CELL DEATH
Also, reperfusion -> further tissue damage due to formation of highly toxic oxygen free radicals = REPERFUSION INJURY

Front 16

Describe some neuro-protective agents being investigated (4)

Back 16

They target the cellular disturbances that --> brain infarct after stroke:
- Glutamate R antagonists --> don't get the excitotoxicity
- Voltage gated Na+ channel blockers -> less Na+ flows into the cells -> less release of glutamate and aspartate
- Voltage-gated Ca2+ ch blockers -> decreased Ca2+ influx
- Free radical scavengers to help with the reperfusion injury
None have been successful yet!

Front 17

What does COX do in a) platelets and b) endothelial cells?

Back 17

Platelets - converts arachidonic acid to thromboxane A2

Endo cells - converts arachidonic acid to PGI2 (prostacyclin) - anti-aggregatory

Front 18

What does aspirin do to COX?

Back 18

Irreversibly binds to it -> blocks COX doing its job

Front 19

What's the effect of low dose daily aspirin on the incidence of cerebrovascular events in people with previous strokes / TIAs?

Back 19

decreased!

Front 20

What dose of aspirin is recommended p/day as secondary prevention in cerebrovascular disease?

Back 20

50-100mg p/day

Front 21

What are the two theories explaining how aspirin inhibits COS in platelets and not endo cells?

Back 21

1. endo cells are able to generate different enzymes to make PGI2
2. Aspirin absorbed by gut -> goes into the portal circulation. Comes into contact with lots of platelets in here -> binds irreversibly to their COX and then they go out into the systemic circulation. But doesn't come into contact with a whole lot of endo cells. Goes through the liver and gets converted to salicylic acid - no effect on COX -> endo cells in systemic circulation aren't affected

Front 22

After a stroke, what are the 'ischaemic penumbra'?

Back 22

The tissue surrounding the irreversibly damaged infarct core. It's still salvagable (doesn't have enough O2 to work properly, but isn't yet at the point of ion pump failure)
This is what we want to try reverse with our therapies

Front 23

Define TIA?

Back 23

Brief episode of neurological deficit due to impaired brain perfusion that resolves within 24 hours by definition (usually resolves within minutes though)

Front 24

After a TIA, what's the risk of stroke in the next week or so?

Back 24

8-10%

Front 25

What is the first and very impt investigation we do when someone presents with stroke?

Back 25

CT HEAD
want to rule out haemorrhage so we can give them tPA

Front 26

What are some investigations the LT suggested you might do when person presents with stroke?

Back 26

First thing to do = CT head
Other things you might do:
- CT angiography (looking for cerebral arterial stenosis/occlusion)
- CT perfusion studies (to define extent of hypoperfusion, help identify extent of the penumbra)
- Carotid and vertebral artery duplex US (looking for stenosis/occlusion)
- Echo - if there's a suspected cardiac source
- CXR, ECG, FBC, EUC, glucose (**), PT, PTT
M
- MRI

Front 27

What is a diffusion weight MRI? What's it used for?

Back 27

Measures the diffusion of water protons in the brain. Able to detect cellular changes associated with acute ischaemic stroke within 30 minutes of onset
*restricted flow will appear BRIGHT on DWI
Bright signals persist for only 10-14 days -> can differentiate between old and recent infarcts

Front 28

Do we use anti-coagulants after a stroke?
Anti-platelet agents?

Back 28

Don't give anti-coagulants

Do use anti-platelet agents (eg aspirin, clopidogrel)

Front 29

Two impt things to monitor in the time post stroke?

Back 29

Glucose
Fever
High temp and high gluocse -> worse outcomes

Front 30

What neuroimaging tool can we use to differentiate between new and old infarcts?

Back 30

diffusion weighted imaging

New infarct - appears bright for about 10-14 days

Front 31

How long from stroke onset until functional recovery is completed in most patients?

Back 31

12 weeks

Front 32

If person has had cardio-embolic stroke, do we want to anti-coagulate them?
Other strokes -> do we anticoagulate?

Back 32

Cardio embolic --> YES do want to anticoagulate (have to wait long enough so you don't precipitate a haemorrhagic transformation)
Other strokes -> don't anti-coagulate

Front 33

To prevent recurrent strokes -> do we work on their BP and cholesterol?

Back 33

Yes

Front 34

Two general functions of the BRF?

Back 34

Arousal/mood setting
Autonomic policeman

Front 35

Where does serotonin come from?

Back 35

The raphe nuclei

Front 36

Five functions of serotonin

Back 36

- Behaviour and our state of reality
- Mood (- there's lots of serotonin in the ventral pre-frontal cortex -> improves our mood)
- Agression (released in the thalamus -> decreased aggressive behaviour)
- Pain (descending pathways to dorsal horn dampen ascending pain information)
- Blood flow control (they wrap around the BVs. Serotonin release -> constriction)

Front 37

Where does ACh come from?

Back 37

BRF ACh groups

Front 38

5 functions of ACh

Back 38

- Arousal (high ICP -> push on the cholinergic nerves -> drowsy)
- Pain (goes down to the dorsal horn and dampens ascending information)
- Memory (projections to the hippocampus and BG)
- ANS control
- Dreaming - cholinergic cells in the pons are active during REM sleep
-

Front 39

Where does dopamine come from?

Back 39

substantia nigra
ventral tegmental area

Front 40

3 functions of DA

Back 40

- Behaviour
- Focusing movements / planning which muscles to use
- Pleasure / motivation

Front 41

Where do noradrenaline come from?

Back 41

Locus coereleus

Front 42

What are the five functions of noradrenaline?

Back 42

- Pleasure / motivation
- ANS control
- BV control
- Neuroplasticity
- Global attention - sensory pathways are heightened

Front 43

Brainstem lesion -> coma. What's affected?

Back 43

The cholinergic cells

Front 44

Brainstem lesion -> nystagmus. What's affected?

Back 44

Vestibular nucleus

Front 45

Brainstem lesion -> speech problems. What's affected?

Back 45

Nucleus ambiguus

Front 46

Brainstem lesion -> hoarse. What's affected?

Back 46

nucleus ambiguus

Front 47

Brainstem lesion -> can only move eyes vertically. What's affected?

Back 47

vertical eye movements = midbrain reticular formation
-> if you can't do horizontal eye movements, it's the pontine RF that's affected

Front 48

What area of the brainstem is responsible for vertical eye movements?

Back 48

Vertical eye movements -> midbrain RF

Front 49

What area of the brainstem is responsible for horizontal eye movements?

Back 49

Horizontal eye movements -> pontine reticular formation

Front 50

What's the one cardinal sign that tells you a person has a brainstem lesion?

Back 50

Pain and temp loss on one side of face and opposite side of the body
(Because spinothalamic crosses in spinal cord -> in brainstem it's contralateral. trigeminal hasnt' crossed yet)

Front 51

What does the superior salivary nucleus give fibres to?

Back 51

Gives para NS fibres to the facial nerve --> submandibular, sublingual, lacrimal and nasal glands

Front 52

What does the inferior salivary nucleus give fibres to?

Back 52

Gives fibres to glossopharyngeal nerve -> parotid gland

Front 53

What do the rostral and caudal parts of the nucleus of solitary tract supply?

Back 53

Caudal = lower -> visceral sensation
Rostal -> taste from VII, IX and X

Front 54

V spinal -> carries what information?

Back 54

Pain and temp from the face

Front 55

V mesencephalic -> carries what information?

Back 55

Proprioception

Front 56

V principle -> carries what information?

Back 56

Tactile touch

Front 57

Describe the cortical innervation of the upper and lower facial nuclei

Back 57

Upper gets bilateral supply
Lower gets only contralateral supply

Front 58

What happens with a unilateral UMNL of the facial nerve?

Back 58

the upper nucleus will get cortical innervation from the other side -> top half of teh face is fine
But the lower nucleus only gets one lot of innervation
==> CONTRAlateral paralysis of bottom half of face

Front 59

where is the facial nerve most commonly damaged?

Back 59

In the stylomastoid foramen

Front 60

What do you see with damage to CN VII?

Back 60

Bell's palsy = paralaysis of that side of the face (top and bottom)

Front 61

Paralysis of L lower face -> where's the lesion?

Back 61

It's an UMNL on the RIGHT side
Lesion could be in the cortex or internal capsule

Front 62

When we say 'lower brainstem' what are we referring to?

Back 62

The pons and medulla

Front 63

What is the highest level of brain / brainstem required to breathe?

Back 63

the pons

Front 64

Which is more impt in regulating breathing - pons or medulla/

Back 64

Pons

Front 65

Does hypoxia information reach the cortex (ie will we be aware of being short of breath)?

Back 65

No

Front 66

What are the two groups of respiratory neurons in the pons? What do they do?

Back 66

Pneumotaxic (higher up. Inhibits inspiration)
Apneustic (lower in pons. Excites inspiratory neurons)

Front 67

What are the three groups of respiratory neurons in the medulla? What do they do?

Back 67

Ventral respiratory group (both inspiratory and expiratory neurons)
Dorsal respiratory group (consists mainly of inspiratory neurons)
Pre-botzinger complex (involved in the pacemaker theory)

Front 68

What is the hering-breuer reflex?

Back 68

Pulmonary stretch Rs in the bronchi and bronchioles. They fire when the lungs inflate -> info carried along X (vagus)
Project to the pneumotaxic centre in the pons -> inhibit inspiration
This decreases the work of breathing (working at the most compliant part of the curve) And prevents over-inflation of lungs

Front 69

What happens to breathing if you cut vagus nerve?

Back 69

Lose the Hering-Breuer reflex
-> don't cut of inspiration as early as you otherwise would --> deep and slow breathing

Front 70

What are the two theories to explain respiratory rhythmogenesis?

Back 70

-Pacemaker theory (pacemaker cells - prebotzinger - in the medulla). Impt in early development / first breath
- Network theory (inspiratory motor neuron from the brainstem is innervating the phrenic nerve -> inspiration. It also goes back and stimulates itself (positive feedback) and also stimulates inhibitory interneuron -> when you reach a threshold, the interneuron will fire and inhibit the motor neuron --> stop inspiration)

Front 71

What's the important TF in the retrotrapezoid nucleus?

Back 71

Phox2b

Front 72

What's the RTN's role / function?

Back 72

Highly sensitive to CO2 - increase respiration in response to hypercapnia

Front 73

What's the RVLM?

Back 73

Rostral ventrolateral medulla
Major source of neurons to the symp outflow (to heart and BVs)
Destroy the neurons here -> massive drop in BP

Front 74

Neuroimagining with CT - > which contrast agent do we use?

Back 74

Iodine

Front 75

Neuro-imagining with MRI -> which contrast agent do we use?

Back 75

Gadolinium

Front 76

What different information do we get from diffusion weighted imaging cf perfusion MRI?

Back 76

DWI - gives us information on cellularity
perfusion MRI -> haemodynamics

Front 77

Will CT straight after infarction stroke show anything?

Back 77

No. Majority of them will still be normal for 3 and even 6 hours after the stroke

Front 78

What are the earliest signs seen on CT after an infarction stroke?

Back 78

Loss of grey-white matter differentiation
Hyperdense MCA sign
Cerebral oedema -> can get mass effect => midline shift and/or ventricular distortion

Front 79

What do we worry about when tissue is perfused after infarction?

Back 79

Haemorrhage. Tissue has softened / is damaged etc - when we reperfuse there's a risk of bleeding

Front 80

What do you see with extra-dural haematoma?

Back 80

D-shaped (convex) projection into the parenchyma

Front 81

What do you see with a subdural haematoma?

Back 81

Crescent shaped / C-shaped WITH the curve of the skull
Also the cerebral sulci become less apparent

Front 82

What sort of blood vessel is usually damaged to --> extradural haematoma?

Back 82

Artery

Front 83

What sort of BV is usually damaged in a subdural haematoma?

Back 83

Vein

Front 84

What sort of pathology / injury is usually associated with an extradural haematoma?

Back 84

Skull fracture

Front 85

What sorts of pathology cause a subarachnoid haemorrhage?

Back 85

Aneurysm rupture = Haemorrhagic stroke
Trauma

Front 86

Where does herpes encephalitis tend to affect first?

Back 86

The frontal lobes

Front 87

How do you differentiate between low and high grade tumours on imaging?

Back 87

Add contrast
Low grade -> no enhancement with contrast
High grade -> enhances eg across the corpus collosum

Front 88

What sort of study is best to answer questions re intervention?

Back 88

Randomised trial

Front 89

What sort of study is best to answer questions re aetiology and prognosis

Back 89

Cohort study

Front 90

What's primary prevention of stroke?

Back 90

Stopping it happening in the first place
Identify people with risk factors and actively treat those factors (eg quit smoking, decrease BP, cholesterol, diabetes, AF etc)

Front 91

What % of total strokes are in people aged over 75?

Back 91

50%

Front 92

What's tertiary prevention with strokes?

Back 92

Goal = to maximise quality of life and prevent further deterioration EG Stroke units

Front 93

What is the rough prognosis of people in the year after stroke?

Back 93

1/3 return to normal functioning
1/3 die
1/3 are permanently disabled

Front 94

Stroke units -> what's the NNT to prevent death?

Back 94

22
(he says this is really good!)

Front 95

What % decrease in deaths do we get with stroke units?
And decrease in death or institutionalisation?

Back 95

17% decrease in death
25% decrease in death / instit

Front 96

Where does stroke rank in terms of most common causes of death?

Back 96

3rd most common cause of death!

Front 97

What are the three factors involved in thrombosis?

Back 97

Hypercoagulability
Endothelial damage
Stagnant blood

Front 98

Describe the pathogenesis of lacunar infarcts

Back 98

Get occlusion of small penetrating arteries. Associated with hypertension --> sclerosis of the BV walls
We get small (20mm) infarcts in deep structures of teh brain (eg basal ganglia, thalamus, internal capsule) and brainstem. Often clinically silent

Front 99

Embolic strokes - do they usually occur in big or small vessels?

Back 99

Large vessels

Front 100

Embolic stroke - which vascular territory are they usually in?

Back 100

MCA (because it's a direct extension of teh internal carotid artery)

Front 101

Do emboli have more or less sudden onset cf thrombi?

Back 101

MORE sudden (in theory. But this isn't always the case in practice)

Front 102

What sorts of places can be the site of origin of emboli?

Back 102

- Heart - AF, valvular disease, past MI
- Stenosis / thrombosis in other vessels eg ICA
- Other less common things - septic embolus, bone marrow embolus (broken femur/hip fracture), air embolus (deep sea diver) amniotic fluid embolism

Front 103

What % of ischaemic strokes and TIAs happen in people with AF?

Back 103

20%

Front 104

Where do we see atherosclerotic plaques causing ischaemic strokes?

Back 104

Start of the internal carotid artery (near bifurcation from the common carotid) = extra cranial artery
Middle cerebral artery
Top and bottom of the basilar artery

Front 105

If you get a thrombus in the internal carotid artery blocking off all blood flow, where will you see the ischaemic territory?

Back 105

In MCA region only
ACA will get colateral supply from the other side (via the atnerior communicating artery)

Front 106

If we have global hypoperfusion, where would we see ischaemia?

Back 106

In the boundary zones (ie water shed areas) - between MCA and ACA and between MCA and PCA

Front 107

What two types of strokes are associated with hypertension?

Back 107

Lacunar infarcts
Intra-cerebral haemorrhage

Front 108

Which BVs are usually involved in intra-cerebral haemorrhage?

Back 108

The small, penetrating BVs

Front 109

What pathologies can -> intra-cerebral haemorrhage?

Back 109

Hypertension is the big one
Other possibilities =
- Vascular malformation
- Haemorrhage into a brain tumour
- Vascular amyloids

Front 110

What are the most common sites for hypertensive haemorrhage?

Back 110

(Intra-cerebral haemorrhage)
BG
Thalamus
Cerebellum
Pons

Front 111

What does an intra-cerebral haemorrhage look like when it's resolved?

Back 111

A 'slit'
Lined with haemosiderin laden macrophages

Front 112

What is sub-arachnoid haemorrhage (non-traumatic) usually due to ?

Back 112

Rupture of Berry Anneurysm

Front 113

Most common sites of berry anneurysms?

Back 113

Acomm
Pcomm
MCA

Front 114

What % of the population have Berry aneurysms approx?

Back 114

2%

Front 115

Berry aneurysm bigger than 1cm -> what's your chance of bleeding each year?

Back 115

50%

Front 116

What are some risk factors for the formation of intracranial aneurysms?

Back 116

Atherosclerotic disease
Congenital anomalies in cerebral BVs
Polycystic kidney disease
Connective tissue disorders (eg Marfans_

Front 117

What are some risk factors for rupture of intra cranial aneurysms?

Back 117

HT
Cigarette smoking
EtOH
Sudden increase in BP

Front 118

How do we tell the difference between an ischaemic and a haemorrhagic stroke?

Back 118

CT scan!

Front 119

What are risk factors for strokes?

Back 119

Age
HT
Diabetes
High cholesterol
Smoking
Alcohol
Positive fam history
No exercise
Cardiac disease (AF, valvular disease, PFO, low ejection fraction)
Prior history of stroke or other vascular disease

The risk factors don't just add up! They multiply

Front 120

What happens to your stroke risk every 10 years?

Back 120

It doubles

Front 121

What is the most important modifiable risk factor for strokes?

Back 121

Hypertension

Front 122

For how long after the stroke is tPA approved for use?

Back 122

4.5 hours after the stroke

Front 123

Why is there a time limit on when you can use tPA post a stroke?

Back 123

After the recommended 4.5 hours, the brain is too soft -> BVs aren't well supported --> high risk of a brain bleed

Front 124

What are the risks associated with giving tPA?

Back 124

Increases your risk of haemorrhage (intra-cranial or systemic)

Front 125

What are some contra-indications for the use of tPA?

Back 125

- Obviously - evidence of haemorrhage in the brain
Also, Hx of previous intracranial haemorrhage
Active internal bleedign
arterio-venous malformation
abnormal platelet or coag studies
Uncontrolled hypertension

Front 126

In the acute setting after an ischaemic stroke, do we want to decrease their BP?

Back 126

No. The only way their brain is getting adequate blood supply is due to the increased perfusion pressure
Would only think about treating it if the high BP was likely to be doing damage to other organs

Front 127

After a haemorrhagic stroke, do we want to treat their high BP?

Back 127

YES definitely. The high BP is what's causing the problem in many cases